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PhD Position in Optogenetics - Barbara Di Ventura - University of Freiburg

PhD position in Optogenetics

Studying NF-κB signalling in health and disease combining optogenetics and mathematical modelling

The NF-κB signalling network is highly complex, operative in most cell types, integrating signals from receptors, co-stimulators, and metabolites (e.g. glutamine). In the canonical pathway, the activation of NF-κB1 depends on the activation of an upstream kinase (IKK), which in turns triggers the degradation of IκBα, the cytosolic inhibitor of NF-κB1. As a consequence, NF-κB1 can enter the nucleus and transcribe its targets, among which IκBα itself. The fact that NF-κB1 activates transcription of its own inhibitor establishes a negative feedback loop that leads to NF-κB1 oscillations. Although much is known about the components of canonical signalling of NF-κB, its detailed spatio-temporal regulation is not well understood. This project aims at engineering optogenetic control of NF-κB1 using different existing approaches based on the blue light sensing LOV2 domain. The developed opto-NF-kB1 will then be used in collaboration with the laboratories of Prof. Dr. Bodo Grimbacher (University Hospital) and Prof. Dr. Jens Timmer (Institute of Physics) to understand at the quantitative level how protein dynamics regulate downstream target genes.

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